Letters to the Editor

Letters to the Editor are welcomed. They may report new clinical or laboratory observations and new developments in medical care or may contain comments on recent contents of the Journal. They will be published, if found suitable, as space permits. Like other material submitted for publication, letters must be typewritten, double-spaced, and must not exceed two typewritten pages in length. No more than five references and one figure or table may be used. See Information for Authors for format of references, tables, and figures. Editing, possible abridgment, and acceptance remain the prerogative of the Editors.

Breast Cancer Metastasis to the Gasserian Ganglion

To the Editor: In an autopsy study of 309 patients with breast carcinoma metastases to the central nervous system, the brain was most frequently affected, followed by the meninges and the spinal cord.1 In this letter, we describe a patient with breast cancer who had metastatic tumor in the gasserian ganglion. A 37-year-old woman came to her oncologist with numbness on the right side of her face of 1 months duration. Several years before, she underwent right modified radical mastectomy followed by adjuvant chemotherapy and locoregional radiotherapy for stage IIIA breast cancer. More than 1 year later, she was treated by radiation for palliation of symptomatic osseous metastatic disease in the spine. On physical examination, sensation was significantly impaired in all three divisions of the fifth cranial nerve on the right side. The presence of metastatic neoplasm in the gasserian ganglion area (right side) of the skull base was demonstrated (Fig. 1, A and B) by MRI. After intracranial clivus metastasis was diagnosed, 4 mg dexamethasone (3 times daily p.o.) and local irradiation was started. After completion of radio-

Sagittal (A) and coronal (B) postcontrast T1-weighted MRI show an enhancing right gasserian ganglion mass (arrows). therapy (30 Gy/10 fractions), there was some degree of improvement of the hemifacial sensory dysfunction. The patient died of her illness 5 months later. In a report of 10 patients with breast cancer with metastatic tumor causing cranial nerve palsies in the absence of intracranial tumor, Hall et al2 found extensive disease at the skull base compressing the nerves; there was no instance of trigeminal ganglion involvement. Metastatic tumor involving the gas-

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serian ganglion was reported by Power in 1886 and then by Parves-Stuart in 1927.3 Iniguez et al4 described a case of neuropathy of the chin as the presenting symptom of breast cancer; the manifestation was explained on the basis of a metastatic lesion in the trigeminal ganglion shown on MRI as enlargement of the gasserian ganglion (an exhibited abnormality akin to that of our patient). Other reported manifestations of the secondary affliction are paresthesia of the mental and infraorbital regions or unilateral decreased sensation to pinprick in all three divisions of the fifth cranial nerve. Radiotherapy is the treatment of choice for skull base metastases because it is effective in achieving palliation5 (such therapy was partly successful in our case). The role of surgery or chemotherapy for this special disease condition is not well established. In conclusion, the trigeminal ganglion is a rare site of metastasis. Oncologists should have a heightened awareness of the unpredictable behavior of carcinoma of the breast, particularly in terms of body locations of neoplastic spread. This example represents only the second case known to us to be reported in the English literature. Thus, definitive conclusions concerning therapeutic management and prognosis have not been ascertained. The unique occurrence of metastatic tumor in the gasserian ganglion was a preterminal event in our patient. Federico L. Ampil, MD Gary V. Burton, MD Mardjohan Hardjasudarma, MD Travis Henley, MD
Departments of Radiology and Medicine Louisiana State University Health Sciences Center Shreveport, LA

3. Willis RA. The spread of tumours in the human body. St. Louis, CV Mosby, 1952, p. 257. 4. Iniguez C, Mauri JA, Larrode P, et al. Mandibular neuropathy due to infiltration of the gasserian ganglion. Rev Neurol 1997;25:10921094. 5. Greenberg HS, Deck MDF, Vikram B, et al. Metastases to the base of skull: clinical findings in 43 patients. Neurology 1981;31:530 537.

Hyperglycemia in an Elderly Diabetic Patient: Drug-drug or Drugdisease Interaction?

To the Editor: The use of gatifloxacin is increasing as the result of convenient dosing and efficacy in a wide range of infectious diseases. Gatifloxacin is generally well tolerated; however, recently there have been several reports of alterations in glucose levels in patients receiving gatifloxacin. An 80-year-old male with a medical history significant for type 2 diabetes mellitus, hypertension, coronary artery disease, hypothyroidism, and benign prostatic hypertrophy presented to the emergency room (ER) with a complaint of elevated blood sugar. Medications included 2.5 mg glipizide, 400 mg gatifloxacin, 25 mg metoprolol, aspirin, 0.075 mg levothyroxine, 10 mg felodipine, 5 mg finasteride, 20 mg omeprazole, and 25 mg hydrochlorothiazide. He was discharged from the hospital 10 days previously after a 3-day inpatient stay for pneumonia. Initial antibiotic therapy was ceftriaxone and azithromycin that was changed to 400 mg gatifloxacin p.o. daily at discharge. During his hospitalization, his random blood glucose ranged from 93 mg/dL to 152 mg/dL. His most recent HgbA1c 2 months before admission was 5.4%. One day before this presentation he noticed lightheadedness, and he found that his glucose was elevated. His glucose in the ER was 510 mg/dL. Other laboratory values of note were a blood urea nitrogen level of 35 mg/dL and a serum

References
1. Tsukada Y, Fouad A, Pickren JW, et al. Central nervous system metastases from breast carcinoma: autopsy study. Cancer 1983;52: 23492354. 2. Hall SM, Buzdar AU, Blumenschein GR. Cranial nerve palsies in metastatic breast cancer due to osseous metastasis without intracranial involvement. Cancer 1983;52:180184.

creatinine level of 2.1 mg/dL. He was treated with intravenous fluids, subcutaneous regular insulin, and discharged with instructions to complete the course of gatifloxacin at a reduced dose of 200 mg p.o. daily. He continued to have elevated blood sugar at home and he returned to the ER 2 days after being released. His glucose level at this visit was 516 mg/dL. On examination, a temperature of 97.9, a pulse of 78 beats per minute, a respiratory rate of 16 breaths per minute, blood pressure of 117/62 mm Hg, and a normal physical examination were noted. The patient reported no change in any of his medications other than gatifloxacin, and there was no noticeable change in diet or exercise. He was treated with intravenous fluids and subcutaneous regular insulin, and the gatifloxacin was stopped. With this modification, his repeat random blood glucose levels were 488 mg/dL, 260 mg/dL, and 187 mg/dL on three occasions over the next week. Gatifloxacin has a broad spectrum of activity, with a wide range of clinical utility. A few case reports indicate that both hypoglycemia and hyperglycemia can be associated with this agent.1 4 In our case, decreased creatinine clearance along with higher doses of gatifloxacin might have contributed to the accumulation of the drug, with worsening of hyperglycemia. The mechanism of hyperglycemia associated with gatifloxacin is currently unknown. The relationship of gatifloxacin and glucose control supports gatifloxacin as the cause, as does the improvement in glucose control after gatifloxacin therapy was discontinued. The Naranjo probability scale suggests a possible drug-related event.5 In conclusion, gatifloxacin therapy may precipitate severe hyperglycemia in patients with diabetes, especially in the elderly population. Awareness of this complication will allow us to anticipate and prevent hyperglycemia. Clinicians should educate their diabetic patients to this possible side ef 2006 Southern Medical Association

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fect and encourage more frequent glucose monitoring while they are taking gatifloxacin. Ravi K. Bobba, MD Edward L. Arsura, MD, FACP
Department of Internal Medicine Veterans Affairs Medical Center, University of Virginia Roanoke-Salem Program, VA

References
1. Khovidhunkit W, Sunthornyothin S. Hypoglycemia, hyperglycemia, and gatifloxacin. Ann Intern Med 2004;141:969. 2. Happe MR, Mulhall BP, Maydonovitch CL, et al. Gatifloxacin induced hyperglycemia. Ann Intern Med 2004;141:968969. 3. Arce FC, Bhasin RS, Pasmantier R. Severe hyperglycemia during gatifloxacin therapy in patients without diabetes. Endocr Pract 2004; 10:404. 4. Donaldson AR, Vandiver JR, Finch CK. Possible gatifloxacin-induced hyperglycemia. Ann Pharmacother 2004;38:602605. 5. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239245.

Please see Reamer L. Bushardts editorial on page 10 of this issue.

Serum Lipid Profile in Postmenopausal Women with Osteoporosis or Osteopenia

To the Editor: Clinical studies have suggested that atherosclerosis is also associated with reduced bone density. Data propose that lipid oxidation, which plays such a central role in the pathogenesis of atherosclerosis, may also promote osteoporosis, thereby linking lipid metabolism and inflammation to regulation of bone density.1 We performed a study to determine the relationship between serum lipid profile values, bone mineral density (BMD) scores and serum osteocalcin levels of postmenopausal women with osteopenia or osteoporosis. Five hundred and fifty postmenopausal women with osteopenia or osteo-

porosis were voluntarily enrolled in this study from September 2000 to March 2005. BMD of the left proximal femur (the femoral neck, the greater trochanter, and Ward triangle) and lumbar spine (L1L4) was measured by duel energy x-ray absorptiometry (DXA) using a QDR-4000 scanner (Hologic Inc., Waltham, MA). Serum total cholesterol, triglyceride levels, low-density lipoprotein cholesterol (LDL-c), low serum high-density lipoprotein cholesterol (HDL-c), very low-density lipoprotein cholesterol, and osteocalcin analysis were performed at the University Hospital Biochemistry Laboratory. According to the data analysis, HDL-c showed a significant positive correlation with a DXA score of the lumbar spine (r 0.12, P 0.05) and hip (r 0.17, P 0.01). Furthermore, a negative correlation was determined between LDL-c and DXA score at the hip (r 0.11, P 0.05). On the other hand, a significant negative correlation was found between osteocalcin values with total cholesterol (r 0.13, P 0.05) and triglycerides (r 0.12, P 0.05) and age (r 0.10, P 0.05). Negative correlation was detected between age with DXA score of the spine (r 0.16, P 0.01) and femur (r 0.32, P 0.01). The positive correlation was found between body mass index with a DXA score of the lumbar spine (r 0.23, P 0.01) and femur (r 0.29, P 0.01). However, no association of other variables was found (P 0.05). There was negative correlation between duration of menopause with a DXA score of the lumbar spine (r 0.19, P 0.01), femur (r 0.31, P 0.01) and serum osteocalcin (r 0.11, P 0.05). The original observation suggesting that oxidized lipids might play a role in bone cell function was the inhibition of osteoblastic differentiation upon treatment with certain oxidized lipids and lipoproteins. A study demonstrated decreased bone mineralization in the vertebrae of mice fed with an atherogenic high-fat diet.1 Furthermore, a prospective study by Chan

et al demonstrated that lipid-lowering therapy resulted in slight increases in osteocalcin without changes in C-terminal telopeptides of type I collagen, also suggesting a direct influence of serum cholesterol on osteoblast function.2 Yamaguchi et al performed a study in 214 postmenopausal women and reported a positive correlation between serum HDL-c levels and DXA scores and a negative correlation between serum LDL-c levels and DXA scores. They also found that serum triglyceride levels were lower in women with vertebral fractures than in those without fracture.3 Tanko performed a study in 340 postmenopausal women and suggested that the weak associations between spine BMD and serum cholesterol can be explained by the fact that both variables are simultaneously affected by estrogen deficiency rather than by a direct influence of serum cholesterol on osteoblast function.4 Andrea et al studied 1,303 postmenopausal women and reported that postmenopausal women with increased plasma LDL cholesterol levels had a greater probability of being classified as osteopenic than women with normal plasma LDL cholesterol levels.5 We also found a positive correlation between DXA scores and HDL-c values, and a negative correlation between cholesterol and triglyceride levels with serum osteocalcin. Thus, our results suggest that there are weak associations between BMD and serum lipid levels. However, vertebral or other skeletal fractures and biochemical markers for bone formation and resorption were not evaluated in this study. It appears that further studies are needed to investigate the relationship between osteoporosis and the lipid profile. Gulcan Gurer, MD Omer Faruk Sendur, MD Ali Aydeniz, MD
Department of Physical Therapy and Rehabilitation Adnan Menderes University Medical School Aydin, Turkey

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References
1. Parhami F, Tintut Y, Beamer WG, et al. Atherogenic high fat diet reduces bone mineralization in mice. J Bone MineralRes 2001; 16:182188. 2. Chan MH, Mak TW, Chiu RW, et al. Simvastatin increases serum osteocalcin concentration in patients treated for hypercholesterolaemia. J Clin Endocrinol Metab 2001;86:45564559. 3. Yamaguchi T, Sugimoto T, Yano S, et al. Plasma lipids and osteoporosis in postmenopausal women. Endocr J 2002;49:211217. 4. Tanko LB, Nielsen SB, Christiansen C. Does serum cholesterol contribute to vertebral bone loss in postmenopausal women? Bone 2003;32:814. 5. Poli A, Bruschi F, Cesana B, et al. Plasma low-density lipoprotein cholesterol and bone mass densitometry in postmenopausal women. Obstet Gynecol 2003;102:922926.

Response to HypoglycemiaAn Enigmatic Dilemma

I agree with Dr. Ranjodh Gill, author of the editorial published in the July 2005 issue of the Southern Medical Journal entitled HypoglycemiaAn Enigmatic Dilemma, that for best diagnostic yield, patients should undergo testing during an episode of spontaneous hypoglycemia.1 In addition, I contend that this includes taking simultaneous blood samples not just for insulin levels, but also for cortisol levels, in light of the fact that spontaneous hypoglycemia may be a presenting feature of secondary hypoadrenalism.2 O. M. P. Jolobe, MRCP
Manchester Medical Society Manchester, United Kingdom

the case report by Dr. H. A. Tran published in the July 2005 issue of the Southern Medical Journal.1 I would add that emergency treatment of intractable hyperkalemia should include not only routine measures such as calcium gluconate and insulin and glucose infusion, as mentioned by the author, but also intravenous sodium bicarbonate and -adrenergic agonists, the latter parenterally or by nebulization.2 There may also be a place for empiric treatment with parenteral hydrocortisone when the biochemical profile is compatible with hyporeninemic hypoaldosteronism and risk factors for this condition are present. This was the case in a patient who was being treated with the heparin analogue pentosan polysulfate in the presence of nephrocalcinosis and in whom hyperkalemia remained refractory, not only to intravenous calcium gluconate, insulin, and glucose, but also to the cation exchange resin calcium resonium. Only on the fourteenth day, when she was coprescribed intravenous hydrocortisone, sodium bicarbonate infusion, and nebulized albuterol, did her plasma potassium fall from 7.2 mmol/L to 3.4 mmol/L.3 Arguably, the therapeutic contribution of hydrocortisone was attributable to its mineralocorticoid action, given the fact that mineralocorticoids ameliorate hyperkalemia in hyporeninemic hypoaldosteronism.4,5 O. M. P. Jolobe, MRCP
Manchester Medical Society Manchester, United Kingdom

5. De Fronzo RA. Hyperkalemia and hyporeninemic hypoaldosteronism. Kidney Int 1980;17: 118134.

Primary Sternal Osteomyelitis Caused By Actinomyces israelii

To the Editor: Primary sternal osteomyelitis (PSO) is a rare entity. Diagnosis is usually difficult due to the nonspecific clinical picture and late radiological findings. We describe a case of PSO due to Actinomyces israelii and how ultrasonography (US), CT, and MRI helped to make the diagnosis and guide treatment. A previously healthy 50-year-old woman without history of trauma presented with painful presternal swelling and fever. A 5-cm warm, fluctuating mass overlying the sternal manubrium was palpated. There was leukocytosis with neutrophilia. Blood cultures were sterile. A chest x-ray was normal. On US, thickening of the insertion of the right pectoralis major muscle on the manubrium, an adjacent heterogenous hypoechoic collection, and irregularities of the contour of the sternum were detected. An US-guided aspiration yielded purulent material. A contrast-enhanced CT demonstrated hypodense soft-tissue swelling, with enhancement surrounding the sternum and right chondrosternal joint. She was unresponsive to cloxacillin and surgical debridement. A MRI showed an extensive involvement of the sternal manubrium with decreased signal intensity on T1-weighted images (T1-WI) and increased signal on T2-WI of the bone marrow, progression of the cortical erosions involving the anterior and posterior aspects of the sternum, and the 2nd 4th chondrosternal joints, with associated pleural thickening. Right pectoralis major muscle and peristernal soft tissues appeared thickened and hypointense on T1-WI (Fig. 1). Culture of the bony material yielded A israelii. She was treated with IV penicillin
2006 Southern Medical Association

References
1. Tran HA. Extreme hyperkalemia. South Med J 2005;98:729732. 2. Singer GS, Brenner BM. Fluid and electrolyte disturbances. In Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, Hauser SL, Longo DL (eds): Harrisons Principles of Internal Medicine Chapter 49, 14th ed, McGraw-Hill Health Profession Division, New York, 1998. 3. Jolobe OMP. Hyperkalaemic paralysis (letter). Age Ageing 2003;32:556557. 4. Orth DN, Kovacs WJ. The Adrenal Cortex. In Wilson JD, Foster DW, Kronenberg HM, Larsen PR (eds): Williams Textbook of Endocrinology, 9th ed, WB Saunders Co, Philadelphia, 1998.

References
1. Gill R. Hypoglycemia-an enigmatic dilemma. South Med J 2005;98:679. 2. Jolobe OMP, Htin TS. Hyponatraemia and spontaneous hypoglycemia. Postgraduate Medical Journal 1997;73:675677.

Extreme Hyperkalemia
To the Editor: Hyporeninemic hypoaldosteronism was one of the postulated mechanisms mediating hyperkalemia in

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Fig. Sagittal T1-weighted MR image reveals extensive involvement of the sternal manubrium with decreased bone marrow signal intensity and cortical erosions involving the anterior and posterior aspects of the manubrium. There is a hypointense soft-tissue swelling in the pre- and retrosternal regions, as well as pleural thickening.

G and extensive surgical debridement, guided by MRI findings, leading to quick disappearance of the fever and improvement of the presternal swelling. Dental caries and periodontal disease of the first and second molar teeth bilaterally were identified. These teeth were removed, and anaerobic bacteria, but not A israelii, were isolated. On the sixth week of treatment she was discharged afebrile on oral antibiotherapy. Most cases of sternal osteomyelitis are complications of sternotomy or thoracic trauma, and less frequently are secondary to spread from contiguous foci.1 PSO is caused by hematogenous dissemination, usually in the setting of IV drug abuse or immunosuppression. Most cases of PSO are caused by Staphylococcus aureus, Gram negative bacteria, Candida, and Aspergillus sp.2 Actinomyces sp are Gram positive anaerobic bacteria found in the normal oral flora which are involved in oral-cervicofacial infections. They have seldom been reported as the cause of osteomyelitis of the facial bones.3 Periodontal disease, damage to mucosal barriers, aspiration, and immunosuppression are risk factors.

A breach in the oral mucosa leads to its introduction into the soft tissues, from where it may spread to the facial bones in a contiguous fashion. In our patient the presumptive portal of entry for A israelii was oral and an ulterior hematogenous seeding probably caused the sternal infection. The ongoing penicillin treatment, together with the difficulties inherent to the culture of Actinomyces may have prevented its isolation from the teeth. Diagnosis of sternal osteomyelitis is straightforward in cases secondary to sternotomy or trauma and bone destruction on x-rays. However, PSO is often difficult to diagnose due to the nonspecific symptoms and late radiological changes. Plain film findings, which lag 1 to 2 weeks, include increased density, displacement of soft tissues, and bone loss.1,2 Technetium-99 scintigraphy is positive earlier and has a good sensitivity, but lacks specificity.4 Despite the limitations of US in the assessment of bone, in our case, the irregularities of the sternal contour and the inflammatory changes of the muscles raised suspicion of osteomyelitis and prompted

further evaluation. CT may show a peristernal soft-tissue mass, periostitis, and bone destruction. But occasionally, it may be difficult to distinguish inflammatory soft-tissue infection with reactive periostitis from true PSO. In such cases, MRI provides better visualization of soft-tissue planes and inflammatory changes in the bone, an excellent resolution, and multiplanar capacity that allow precise delineation of the extent of soft tissue and osseous involvement, which are invaluable in the presurgical assessment.4 In our patient, MRI showed a more extensive osseous and soft-tissue involvement, pleural thickening, excluded mediastinum involvement, and enabled surgeons to tailor surgical therapy and achieve a complete debridement. A prompt diagnosis of PSO is essential for appropriate treatment and to avoid extension to the mediastinum. US may have a role in the assessment of sternal abnormalities, and provides an accessible means of obtaining tissue samples. Both CT and MRI are extremely useful in the diagnosis, but we favor MRI as the method of choice for assessing its extension and for surgical planning. I. Pinilla, MD, PhD C. Mart n-Herva s, MD, PhD E. Gil-Garay, MD, PhD
Departments of Radiology and Orthopedic Surgery Hospital Universitario La Paz Madrid, Spain

References
1. Franquet T, Gime nez A, Alegret X, et al. Imaging findings of sternal abnormalities. EurRadiol 1997;7:492497. 2. Lin JC, Miller SR, Gazzaniga AB. Primary sternal osteomyelitis. Ann Thorac Surg 1996; 61:225227. 3. Yenson A, deFries HO, Deeb ZE. Actinomycotic osteomyelitis of the facial bones and mandible. Otolaryngol Head Neck Surg 1983; 91:173176. 4. Moylett E, Chung T, Baker C. Magnetic resonance imaging in a child with primary sternal osteomyelitis. Pediatr Infect Dis J 2001;20: 547550.

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Distribution of Pleural Effusion in Congestive Heart Failure

To the Editor: The recent article by Woodring questioned the classic statement of predominantly rightsided pleural effusions in patients with congestive heart failure (CHF), on the basis of a study of 120 patients whose cardiac pleural effusions were equally distributed between the right and the left hemithorax.1 More importantly, the author also concluded that left-sided effusion is not an atypical finding in CHF and is not, in and of itself, an indication for further clinical or imaging workup to find alternative causes. This latter point seems to contradict Lights recommendations2 and consensus guidelines,3 and may possibly influence practice trends. Therefore, we present our own experience with the radiographic distribution of cardiac pleural effusions in the largest clinical series to our knowledge. In the last 12 years, we identified 221 of 1,515 consecutive patients who underwent diagnostic thoracentesis as having CHF, at the University Hospital Arnau de Vilanova (Lleida, Spain). The diagnosis of CHF was established by clinical criteria (presentation, pleural fluid characteristics, and response to therapy). Twenty-four patients were excluded from the analysis because pos-

teroanterior chest x-rays were not performed or available. The final analysis group of 197 patients consisted of 98 (50%) males and 99 (50%) females, with a mean age of 77 9 years. As shown in the Table, we found a statistically significant difference in the distribution of pleural effusion between the right and left hemithorax (102 versus 39, 2 27.26, P 0.001), even when considering only unilateral effusions (62 versus 18, 2 24.20, P 0.001). Seventy-seven percent of patients had effusions that occupied a third or less of the hemithorax in the posteroanterior radiographic view. When four clinical series comprising 441 patients with CHF are combined,1,4,5 304 (69%) patients had bilateral pleural effusions, 95 (21%) had unilateral right-sided effusions, and 42 (9%) had unilateral leftsided effusions (Table). However, radiographic identification of pleural effusion is insensitive and detects only moderate to large amounts of pleural fluid. In a study of 60 patients with decompensated CHF, chest CT was used as the gold standard for the presence or absence of pleural effusion.6 As many as 52 (97%) of the 60 patients had pleural effusion; of these, 23 (44%) had equally bilateral effusion, 20 (38%) had right-sided predominant bilateral effusion, 2 (4%) had left-sided predominant bilateral effusion, 5 (10%) had rightsided effusion only, and 2 (4%) had leftsided effusion only. Again, 2 analysis

shows a statistically significant difference between the right and left hemithorax (25 versus 4, 2 15.20, P 0.001). To conclude, pooled data demonstrate a great preponderance of bilateral pleural effusions in CHF, and approximately double numbers of unilateral pleural effusions on the right side than on the left. For this reason, contrary to the suggestion of Woodring, we think that in the context of CHF thoracentesis is indicated if more than a minimal unilateral effusion (particularly left-sided) exists. Acting on Woodrings advice may provide clinicians false reassurance when evaluating patients with unilateral left-sided effusions in the setting of heart disease, thus missing important causes of exudative pleural effusions such as pericardial disease, postcardiac injury syndrome or postcoronary artery bypass surgery, as well as comorbid conditions such as pulmonary embolism or pneumonia. Jose M. Porcel, MD
Department of Internal Medicine Arnau de Vilanova University Hospital Lleida, Spain

Manuel Vives, MD
Division of Internal Medicine Cl nica Recoletas Albacete, Spain

References
1. Woodring JH. Distribution of pleural effusion in congestive heart failure: what is atypical? South Med J 2005;98:518523.

Table. Published series on the distribution of cardiac pleural effusions assessed by chest radiographya Current series
Right Left Bilateral R L Bilateral R L Bilateral L R Total
a b

Woodring, 20051
18 (15) 15 (12,5) 25 (21) 36 (30) 26 (22) 120

Peterman and Brothers, 19834

2 (4) 3 (5,5) 16 (30) 19 (35) 14 (26) 54

Sum of previous seriesb

82 (22) 36 (10) 81 (22) 111 (30) 61 (16) 371

Weiss and Spodick, 19845

13 (19) 6 (9) 51 (73) 70

Sum of all seriesc

95 (21) 42 (9) 304 (69) 441

62 (31) 18 (9) 40 (20) 56 (28) 21 (11) 197

Data are presented as No. (%). R right; L left. Difference between the right and left side is significant (163 vs 97, 2 16.75, P0.001). c Difference between unilateral right and left side is significant (95 vs 42, 2 20.5, P0.001).

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2. Light RW. Pleural effusion. N Engl J Med 2002;346:19711977. 3. Maskell NA, Butland RJ, Pleural Diseases Group, Standards of Care Committee, British Thoracic Society. BTS guidelines for the investigation of a unilateral pleural effusion in adults. Thorax 2003;58 (Suppl 2):ii817. 4. Peterman TA, Brothers SK. Pleural effusions in congestive heart failure and in pericardial disease. N Engl J Med 1983; 309:313. 5. Weiss JM, Spodick DH. Laterality of pleural effusions in chronic heart failure. Am J Cardiol 1984;53:951. 6. Kataoka H. Pericardial and pleural effusions in decompensated chronic heart failure. Am Heart J 2000;139:918923.

Localized Amyloidosis of Cardiac and Skeletal Muscle: Investigate Promptly Where It Manifests
To the Editor: A negative biopsy may not rule out amyloidosis, as seen in the following case. We report the case of a patient with cardiac and muscular manifestations of amyloidosis, who had a normal rectal mucosal biopsy. The diagnosis of amyloidosis was only established at autopsy. A 58-year-old male was admitted with pulmonary edema. He had experienced lower limb weakness, muscle cramps, and easy fatigability for 2.5 years, and had a 6 month history of shortness of breath. In addition, he had a history of arterial hypertension and was a previous smoker. Clinical examination revealed pulmonary rales and leg edema. Electrocardiography showed Q-waves in the posterolateral leads. Chest x-ray revealed pulmonary congestion. Troponin-T (semiquantitatively) and creatine kinase (188 U/L, normal 80 U/L) were elevated. Coronary angiography revealed a 90% stenosis of the left anterior descending artery. Echocardiography (Fig.) showed a thickened, echodense left ventricular myocardium (13 mm, normal 11 mm) and an enlarged left atrium (43 mm, normal 40 mm). Systolic func-

tion was normal (fractional shortening 25%), but pulsed wave Doppler sonography of the transmitral flow showed a deceleration time of less than 150 milliseconds and an E-velocity of 1.16 m/s with an E/A ratio 2, indicating restrictive cardiomyopathy. Dipyridamol stress echocardiography revealed reversible hypokinesis of the midseptal and apicoseptal segments, and coronary bypass grafting was considered. The patient was discharged with acetylsalicylic acid, metoprolol and ramipril. The patients restrictive cardiomyopathy was suspected to be due to amyloidosis since there were no indications for endomyocardial fibrosis, sarcoidosis, hemochromatosis, Fabry or Gaucher disease, Hurler syndrome, or glycogen storage disease. Bone marrow aspiration revealed 20% plasma cells. Immunohistochemistry exhibited a dominance of -positive plasma cells, but no evidence of clonal light-chain restriction, being confirmed by a polyclonal pattern of immunoglobulin gene rearrangement on polymerase chain reaction for the VDJ heavy chain locus. Due to complaints of dizziness, muscle pain in the limbs, weakness of the upper eyelids and chewing muscles after physical stress, as well as worsening heart failure, the patient was readmitted after 10 weeks. Clinical examination revealed massive peripheral edema, dyspnea, and a weight gain of 8 kg. Creatinine was 1.6 mg/dL (normal 1.1 mg/dL) and creatine-kinase was repeatedly elevated (80 103 U/L, normal 80 U/L). Serum troponin-T was normal. Brain natriuretic peptide was 11,070 pg/mL (normal 227 pg/mL). Fractional shortening had deteriorated to 15% (normal 24%). Systolic blood pressure was 80 mm Hg. Rectal biopsy, light chains, and Bence-Jones protein were negative. Considering the bone marrow findings, immunologic and molecular biologic results, and the lack of serologic evidence of gammopathy, plasmacytosis was assumed reactive. Clinical neurologic examination revealed postural tremor, exaggerated tendon reflexes on the lower limbs and

positive Babinski sign. Nerve conduction studies of the left median nerve revealed slightly reduced amplitude of the compound muscle action potential on distal and proximal superficial stimulation. Repetitive stimulation of the left median nerve was normal. Acetylcholine receptor antibodies were normal. Needle electromyography of the right rectus femoral muscle revealed shortened mean motor unit action potential duration. Myopathy and polyneuropathy were suspected and a muscle biopsy was performed. Two days before the muscle biopsy, however, the patient died suddenly at home. Autopsy, confined to histologic examination of the myocardium, showed interstitial deposition of Congo red positive material subendocardially and in the intramyocardial artery walls. Immunohistochemistry revealed a positive staining for antibodies against amyloid P, absent staining with antibodies against amyloid A and no reaction with antibodies against kappa or lambda chains. Due to autolysis, the amyloid could not be further investigated. The patients sister, children, and nephews had normal clinical cardiological examinations, electrocardiographies, and echocardiographies. Amyloidosis may be acquired or hereditary, localized, or systemic.1,2 Most likely the patient suffered from either primary systemic (AL)-amyloidosis or from senile amyloidosis. Rapid progression of the disease, however, favors AL-amyloidosis.2 History and investigations of the relatives excluded familial amyloidosis. Chronic infection was excluded by history and instrumental investigations. Cardiac involvement occurs frequently in AL, hereditary, and senile amyloidosis.3 Deposition of amyloid in the myocardial interstitial space, vessel walls, valves, and conduction system may lead to myocardial thickening, coronary stenosis, valve abnormalities, arrhythmias, and diastolic dysfunction.1,4 A restrictive filling pattern predicts poor outcome.1 It remains uncertain, however, whether the coronary stenosis was due to amyloidosis or arteriosclerosis and whether the patients

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Fig. Echocardiographic recording of the pulsed-wave signal of the transmitral flow,

showing a high E-wave with a short deceleratin time of 150 msec (arrow) and a very small A-wave (asterisk). These abnormalities are indicative of a restrictive filling pattern.

sudden death was due to myocardial ischemia or conduction system affection.4 In our patient, amyloidosis was missed due to the fact that no clinically affected organs were biopsied. (Rectal biopsy in AL-amyloidosis is positive in only 60 89% of cases.) In addition, skeletal muscle affection was neglected, and diagnostic management was too slow, facing the rapid progression and poor outcome of the disease.1 The patient might have profited from heart transplantation if amyloidosis had been detected earlier. As soon as cardiac amyloidosis is suspected, prompt diagnosis is essential. Claudia Sto llberger, MD Christina Steger, MD Marion Avanzini, MD
Second Medical Department Krankenanstalt Rudolfstiftung sterreich Vienna, O

References
1. Falk RH, Comenzo RL, Skinner M. The systemic amyloidosis. N Engl J Med 1997;337: 898909. 2. Kyle RA, Spittell PC, Gertz MA, et al. The premortem recognition of systemic senile amyloidosis with cardiac involvement. Am J Med 1996;101:395400. 3. Dubrey SW, Cha K, Simms RW, et al. Electrocardiography and Doppler echocardiography in secondary (AA) amyloidosis. Am J Cardiol 1996;77:313315. 4. Palladini G, Malamani G, Co F, et al. Holter monitoring in AL amyloidosis: prognostic implications. Pacing Clin Electrophysiol 2001; 24:12281233. 5. Mandl LA, Folkerth RD, Pick MA, et al. Amyloid myopathy masquerading as polymyositis. J Rheumatol 2000;27:949952.

Pedometer-measured Walking and Risk Factors for Disease

To the Editor: Research documenting the health benefits of exercise is convincing, but finding ways to encourage sedentary patients to become more active remains a challenge. Adherence to vigorous, structured exercise programs is particularly low. One generally inactive subgroup is older women, and postmenopausal women who do exercise tend to

Hans Feichtinger, MD
Department of Pathology Krankenanstalt Rudolfstiftung sterreich Vienna, O

Robert Ullrich, MD
Department of Pathology Allgemeines Krankenhaus sterreich Vienna, O

Josef Finsterer, MD
Krankenanstalt Rudolfstiftung sterreich Vienna, O

engage in moderate activity, specifically walking. The goal of this investigation was to document the relationship between daily walking volume (steps per day measured by a pedometer) and selected cardiovascular risk variables in postmenopausal women. Eighty-eight postmenopausal women between the ages of 50 and 75 years volunteered for participation in this institutional-review-boardapproved study at the University of Tennessee. Body composition was determined using a three-compartment model in which bone mineral content (GE Medical Systems, Lunar DPX-NT, Madison, WI) and total body density (air displacement plethysmography, Life Measurement Inc., Concord, CA) were measured. A 10 mL blood sample was obtained in the early morning hours when the subject was in a fasted and rested state. Samples were analyzed in a certified laboratory for total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (Trig), C-reactive protein (CRP), glucose (Glu), and hemoglobin A1C (A1C). Subjects subsequently wore a pedometer for 10 to 14 days, and an average daily step count was determined. Pearson correlations were used to explore the relationship between walking volume and cardiovascular risk variables (SPSS version 11 for Macintosh, Chicago, IL). Partial correlation coefficients were calculated to examine the relationship between walking volume and risk factors while controlling for the effect of body fat percentage (%BF). ANOVA was used to compare the HDL-C values among individuals in different physical activity categories. The average age, %BF, and body mass index of participants was 61.0 5.8 years, 40.2 9.2%, and 27.8 5.9 kg/m2, respectively. Subjects ranged from very inactive (1,300 steps per day) to highly active (14,000 steps per day). The correlation between daily steps and %BF was 0.404 (P 0.001). Walking volume was significantly related to HDL-C, TC to HDL-C ratio, and Trig (see Table).
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Percent BF was significantly correlated with TC to HDL-C ratio and HDL-C (see Table). Glu was significantly related to both %BF (r 0.217, P 0.043) and steps (r 0.289, P 0.006), but there was no relationship between A1C and these variables. CRP was significantly related to %BF (r 0.395, P 0.001) but not steps (r 0.106, P 0.324). After controlling for %BF, daily steps remained significantly related to HDL-C (r 0.247, P 0.016), TC to HDL-C ratio (r 0.284, P 0.008), Trig (r 0.239, P 0.026), and Glu (r 0.226, P 0.035). The most active women, averaging approximately 8,000 steps per day, had a HDL-C of 71.6 2.6 mg/ dL. This was significantly higher (P 0.05) than the HDL-C of women who walked approximately 5,000 steps per day (56.6 2.7 mg/dL). Walking is the most common physical activity chosen by women,1 and the relationship between walking and health outcomes is particularly strong in this group.2,3 This study provides additional

evidence that daily walking is linked to important cardiovascular risk variables. Not surprisingly, these variables were also strongly associated with %BF. These data provide support for the important role that regular walking and weight control play in promoting cardiovascular health in postmenopausal women. Pedometer-monitored programs are effective in helping sedentary individuals become more active.4,5 This may be due to the fact that pedometer-monitored programs use goal setting and self-monitoring as reinforcement. There is evidence that the addition of a pedometer to a brief counseling session by a physician will lead to greater daily walking.5 Given that walking is a generally safe form of aerobic exercise and yields important health benefits, physicians might consider prescribing pedometer-monitored programs for inactive patients. Dixie L. Thompson, PHD Emily M. Krumm, MS Olivera L. Dessieux, MS Pamela Andrews, MS
Center for Physical Activity and Health

Department of Exercise, Sport, and Leisure Studies University of Tennessee Knoxville, TN

References
1. Rafferty AP, Reeves MJ, McGee HB, et al. Physical activity patterns among walkers and compliance with public health recommendations. Med Sci Sports Exerc 2002;34:1255 1261. 2. Thompson DL, Rakow J, Perdue SM. Relationship between accumulated walking and body composition in middle-aged women. Med Sci Sports Exerc 2004;36:911914. 3. Manson JE, Greenland P, LaCroix AZ, et al. Walking compared with vigorous exercise for the prevention of cardiovascular events in women. N Eng J Med 2002;347:716725. 4. Hultquist CN, Albright C, Thompson DL. Comparison of walking recommendations in previously inactive women. Med Sci Sports Exerc 2005;37:676683. 5. Stovitz SD, VanWormer JJ, Center BA, et al. Pedometers and brief physician counseling: increasing physical activity for patients seen at a family practice clinic. Med Sci Sports Exerc 2004;36:S241.

Table. Relationship between blood lipids and daily walking and body fat percentagea TC
Steps %BF 0.122(0.256) 0.085(0.430)

HDL-C
0.358(0.001) 0.338(0.001)

LDL-C
0.188(0.079) 0.186(0.082)

TC/HDL-C
0.373(0.001) 0.314(0.003)

Trig
0.285(0.007) 0.173(0.108)

Values represent Pearson correlation coefficients with the significance level in parentheses. a TC, total cholesterol; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; TC/HDL-C, the ratio of TC to HDL-C; Trig, triglycerides; Steps, average daily steps; % BF, body fat percentage.

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Errata
In the December 2005 issue two authors names were misspelled. In the Table of Contents, the first author under Religious Awareness Training for Medical Students: Effect on the Clinical Behavior should have read John T. Chibnall. The author of the Selected Annotated Bibliography (South Med J 2005;98:12511254) should have read Conrad C. Daly, MTh. We regret these errors. In Socolar RRS, Savage E, Keyes-Elstein L, et al. Factors that affected parental disciplinary practices of children aged 12 to 19 months. South Med J 2005;98:11811191, the following changes should have been made: In Table 2 the following variables are given in percentages: Respondents relationship to child, Maternal race, Paternal race, Maternal education, Cut off for CES-D, Knowledge of Infant Development, Boys, Household income, Maternal marital status, Number of people in household. Also, on the line that reads: Number of people in household (N 167), there is a number 2 to the right of this phrase. This should not be there. The last sentence of the first paragraph was not accurate. It should have read: In addition, the mode of administration, including positive/negative demeanor, consistency, and follow-through, has not been studied.

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